Perioperative outcomes of general versus spinal anesthesia in the lumbar spine surgery population: A systematic review and meta-analysis of data from 2005 through 2021.

Study design: Meta-analysis. Objectives: Perform a systematic review and meta-analysis to determine the perioperative utility of general versus spinal anesthesia in the lumbar spine surgery population. Methods: PubMed and Embase were queried for manuscripts reporting perioperative outcomes for patients undergoing one to three-level lumbar spine surgery (including decompression, fusion, and decompression with fusion) using either general or spinal anesthesia. Inclusion criteria included studies published from 2005 to 2021, in English, involving primary data from human subjects. Studies were further screened for data on total operative time, blood loss, intraoperative hypotension, pain scores, postoperative nausea and vomiting, time required in post-anesthesia care unit (PACU), PACU pain anesthetic requirement, and length of stay. Risk of bias for each study was assessed using standardized tools (i.e., RoB 2, ROBINS-I, NOS, as appropriate). Potential predictors of outcome were compared using univariate analysis, and variables potentially associated with outcome were subjected to meta-analysis using Cochran-Mantel-Haenszel testing to produce standard mean differences (SMD) or odds ratios (OR) and 95% confidence intervals (CI). Results: In total, 12 studies totaling 2796 patients met inclusion criteria. 1414 (50.6%) and 1382 (49.4%) patients underwent lumbar spine surgery with general anesthesia and spinal anesthesia, respectively. Patients undergoing spinal anesthesia were statistically more likely to have coronary artery disease and respiratory dysfunction. Total operative time (SMD: 12.62 min, 95% CI -18.65 to -6.59), estimated blood loss (SMD: 0.57 mL, 95% CI -0.68 to -0.46), postoperative nausea and vomiting (OR = 0.20, 95% CI 0.15 to 0.26), time required in PACU (SMD = -0.20 min, 95% CI -0.32 to -0.08), and length of stay (SMD = -0.14 day, 95% CI -0.18 to -0.10), all statistically significantly favored spinal anesthesia over general anesthesia (p < 0.05). Conclusion: In one to three-level lumbar spine surgery, current literature supports spinal anesthesia as a viable alternative to general anesthesia. As this was a heterogeneous patient population, prospective randomized trials are needed to corroborate findings.

Cerebrospinal fluid and plasma biomarkers in individuals at risk for genetic prion disease.

BACKGROUND: Prion disease is neurodegenerative disease that is typically fatal within months of first symptoms. Clinical trials in this rapidly declining symptomatic patient population have proven challenging. Individuals at high lifetime risk for genetic prion disease can be identified decades before symptom onset and provide an opportunity for early therapeutic intervention. However, randomizing pre-symptomatic carriers to a clinical endpoint is not numerically feasible. We therefore launched a cohort study in pre-symptomatic genetic prion disease mutation carriers and controls with the goal of evaluating biomarker endpoints that may enable informative trials in this population. METHODS: We collected cerebrospinal fluid (CSF) and blood from pre-symptomatic individuals with prion protein gene (PRNP) mutations (N = 27) and matched controls (N = 16), in a cohort study at Massachusetts General Hospital. We quantified total prion protein (PrP) and real-time quaking-induced conversion (RT-QuIC) prion seeding activity in CSF and neuronal damage markers total tau (T-tau) and neurofilament light chain (NfL) in CSF and plasma. We compared these markers cross-sectionally, evaluated short-term test-retest reliability over 2-4 months, and conducted a pilot longitudinal study over 10-20 months. RESULTS: CSF PrP levels were stable on test-retest with a mean coefficient of variation of 7% for both over 2-4 months in N = 29 participants and over 10-20 months in N = 10 participants. RT-QuIC was negative in 22/23 mutation carriers. The sole individual with positive RT-QuIC seeding activity at two study visits had steady CSF PrP levels and slightly increased tau and NfL concentrations compared with the others, though still within the normal range, and remained asymptomatic 1 year later. T-tau and NfL showed no significant differences between mutation carriers and controls in either CSF or plasma. CONCLUSIONS: CSF PrP will be interpretable as a pharmacodynamic readout for PrP-lowering therapeutics in pre-symptomatic individuals and may serve as an informative surrogate biomarker in this population. In contrast, markers of prion seeding activity and neuronal damage do not reliably cross-sectionally distinguish mutation carriers from controls. Thus, as PrP-lowering therapeutics for prion disease advance, "secondary prevention" based on prodromal pathology may prove challenging; instead, "primary prevention" trials appear to offer a tractable paradigm for trials in pre-symptomatic individuals.

Opposing Roles of apolipoprotein E in aging and neurodegeneration.

Apolipoprotein E (APOE) effects on brain function remain controversial. Removal of APOE not only impairs cognitive functions but also reduces neuritic amyloid plaques in mouse models of Alzheimer's disease (AD). Can APOE simultaneously protect and impair neural circuits? Here, we dissociated the role of APOE in AD versus aging to determine its effects on neuronal function and synaptic integrity. Using two-photon calcium imaging in awake mice to record visually evoked responses, we found that genetic removal of APOE improved neuronal responses in adult APP/PSEN1 mice (8-10 mo). These animals also exhibited fewer neuritic plaques with less surrounding synapse loss, fewer neuritic dystrophies, and reactive glia. Surprisingly, the lack of APOE in aged mice (18-20 mo), even in the absence of amyloid, disrupted visually evoked responses. These results suggest a dissociation in APOE's role in AD versus aging: APOE may be neurotoxic during early stages of amyloid deposition, although being neuroprotective in latter stages of aging.